Immunoglobulin single variable domains, such as camelid VHH domains, camelized VH domains or humanized VHH domains, represent a rapidly growing class of antibody therapeutics. For example, immunoglobulin single variable domains against vWF have been described in WO2004/015425, WO2004/062551, WO2006/074947, WO2006/122825, WO2009/115614, and WO2011/067160.
Proteins such as immunoglobulin single variable domains (ISVDs) typically must be stored and transported between initial manufacture and use, e.g. administration to a patient. Transport, manufacture, storage and delivery processes can exert manifold stresses on the immunoglobulin single variable domain, such as chemical and physical stresses. During storage chemical modifications can occur such as, for instance, deamidation, racemization, hydrolysis, oxidation, isomerization, beta-elimination or disulfide exchange. Physical stresses can cause denaturation and unfolding, aggregation, particulate formation, precipitation, opalescence or adsorption.
There remains a need for providing formulations for immunoglobulin single variable domains, e.g. as defined herein, which enhance stability, preserve the active agent against chemical and/or mechanical stress, and hence allow storage and temperature changes without significant physical or chemical deterioration, remain stable for prolonged periods of time, and/or are patient friendly, e.g. in which the active agent is soluble at high concentration.